Terlizzi Vito, Fevola Cristina, Cecchetti Martina, Terminiello Alberto, Curci Franco, Bartolini Elisa, Rubino Chiara, Stinco Mariangela, Carrera Simona, Bonomi Paolo, Taccetti Giovanni, Sellers Zachary M, Indolfi Giuseppe
Meyer Children's Hospital IRCCS, Cystic Fibrosis Regional Reference Centre, Department of Paediatric Medicine, Florence, Italy.
Meyer Children's Hospital IRCCS, Cystic Fibrosis Regional Reference Centre, Department of Paediatric Medicine, Florence, Italy.
J Cyst Fibros. 2025 May;24(3):574-580. doi: 10.1016/j.jcf.2024.12.010. Epub 2025 Jan 12.
Elexacaftor-tezacaftor-ivacaftor (ETI) has significantly improved the clinical course of people with cystic fibrosis (pwCF) and eligible CFTR variants. In this study, we prospectively evaluated liver elastography, liver fibrosis indices and liver tests in children with CF aged 6-12 years started on ETI therapy.
Body mass index, sweat test, percent predicted forced expiratory volume in one second, serum markers of liver injury or portal hypertension, liver fibrosis indices, controlled attenuation parameter and liver stiffness were assessed before starting ETI and three and twelve months post-ETI, according to new international guidelines.
27 children with CF were enrolled, 14 with liver involvement and 13 without liver involvement at baseline. A significant improvement in sweat chloride after ETI was observed in all subjects. In those with liver involvement, liver stiffness significantly decreased at 12 months of ETI, with all individuals achieving normalization or near-normalization of liver stiffness. The majority of individuals with abnormal AST, ALT, GGT, or liver fibrosis indices at baseline experienced normalization by 12 months of ETI (AST: 67%, ALT: 100%, GGT: 50%, APRI: 100%, GPR: 100%). In the no liver involvement group, the only significant change in liver health metrics at 12 months was a significant reduction in platelets (P<0.05) that remained within the normal range.
ETI is associated with improvement in liver stiffness, liver function tests and fibrosis indices in pwCF and liver involvement. ETI may reduce the development of advanced CF liver disease, but longer observations with larger cohorts are needed.
依列卡福妥-替扎卡福妥-依伐卡福妥（ETI）显著改善了囊性纤维化患者（pwCF）及符合条件的囊性纤维化跨膜传导调节因子（CFTR）变体患者的临床病程。在本研究中，我们前瞻性评估了开始接受ETI治疗的6至12岁CF儿童的肝脏弹性成像、肝纤维化指标和肝功能检查。
根据新的国际指南，在开始ETI治疗前、ETI治疗后3个月和12个月时，评估体重指数、汗液试验、一秒用力呼气量预测百分比、肝损伤或门静脉高压的血清标志物、肝纤维化指标、受控衰减参数和肝脏硬度。
纳入了27例CF儿童，其中14例基线时有肝脏受累，13例无肝脏受累。所有受试者在ETI治疗后汗液氯化物均有显著改善。在有肝脏受累的患者中，ETI治疗12个月时肝脏硬度显著降低，所有个体的肝脏硬度均恢复正常或接近正常。大多数基线时AST、ALT、GGT或肝纤维化指标异常的个体在ETI治疗12个月时恢复正常（AST：67%，ALT：100%，GGT：50%，APRI：100%，GPR：100%）。在无肝脏受累组中，12个月时肝脏健康指标唯一的显著变化是血小板显著减少（P<0.05），但仍在正常范围内。
ETI与pwCF及肝脏受累患者的肝脏硬度、肝功能检查和纤维化指标改善相关。ETI可能会减少晚期CF肝病的发生，但需要对更大队列进行更长时间的观察。
